Good glycemic control, lipid control, or blood pressure (BP) control can be achieved by adherence to recommended care, including medication, preventive care, and lifestyle modifications. Good physiologic control, in turn, attenuates risk of progression to acute end-organ disease, such as cardiovascular disease (CVD), or obesity. Many patients, however, are non-adherent with their prescribed treatment protocols and exhibit physiologic dysregulation. Allostatic load is a measure that quantifies cumulative stress-related physiologic dysregulation across multiple body systems. Persistently stressful psychosocial and economic circumstances increase risk of impaired immunologic response, physiologic dysregulation, and end-organ disease. The same factors that influence physiologic dysregulation directly -- financial circumstances (high cost-sharing, economic deprivation), social stress, and personal distress - may also influence physiologic dysregulation indirectly through their effects on non-adherence to recommended care. The primary objective of our proposed study is to test our working hypothesis that adherence to 1) recommended lifestyle and 2) prescribed medication regimen mediates the association of psychosocial stress and personal distress with allostatic load. The principal study population will be 25-59 year old enrollees with Kaiser Permanente Georgia (KPGA) who responded to a 2005 survey on psychosocial circumstances and lifestyle (including leisure physical activity and dietary intake) and who remained enrolled in 2006 for assessment of allostatic load (N=1,915). Consistent with the requirements of PA-06-151, the proposed study will use existing datasets (survey results and computerized administrative data) to create a covariate rich dataset adequately powered to answer an important question unanswered by current models of the association of psychosocial stressors, allostatic load, and disease progression. Is the degree of allostatic load, and its subsequent influence on disease progression, partly mediated by the effects of psychosocial stressors on adherence to a recommended care regimen? PUBLIC HEALTH RELEVANCE: One mechanism by which stressful interpersonal relationships and personal distress and anxiety may contribute to poor health outcomes is through decreasing patient adherence to recommended care. If so, non- adherence to recommended care might be corrected by acknowledging the benefits of social support and stress mitigation in the curriculum of health promotion programs offered through government agencies, community organizations, and both public and private insurance plans.